OBJECTIVES: In ESCAPE-TRD, esketamine nasal spray (ESK-NS) significantly increased the probability of achieving remission at Week 8, and of being relapse‑free through Week 32 after remission at Week 8, versus quetiapine extended release (QTP-XR), in patients with treatment resistant depression (TRD). Here, we assess changes in health-related quality of life (HRQoL), as measured by the QoL in Depression Scale (QLDS).

METHODS: ESCAPE‑TRD (NCT04338321) was a randomized phase IIIb trial comparing ESK-NS and QTP-XR, both alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor, in patients with TRD.

Change from baseline (CfB) in QLDS was analyzed using mixed model for repeated measures. Time to clinically meaningful improvement on the initiated treatment (defined as CfB ≤–8) was analyzed using Kaplan‑Meier and Cox regression estimating hazard ratios (HR) and 95% confidence intervals (CIs). Analyses included all randomized patients, using observed data without imputation from on‑treatment visits and retrieved dropouts after treatment discontinuation (incorporating potential benefit of subsequent treatments). P values reported are not adjusted for multiple testing.

RESULTS: Patients were randomized to ESK-NS (N=336) or QTP-XR (340). At Week 8, a greater CfB in QLDS was observed for ESK-NS (–11.293) versus QTP-XR (–8.337), with a –2.956 difference (95% CI: –4.346, –1.565; p<0.001). At Week 32, CfB was still greater for ESK-NS (–14.743) relative to QTP-XR (–12.435), corresponding to a −2.308 difference (95% CI: –3.827, –0.789; p=0.003).

Most patients reported a clinically meaningful improvement (ESK-NS: 81.5%, QTP‑XR: 66.8%), with a shorter time to meaningful improvement with ESK-NS versus QTP‑XR (median 1.018 versus 1.906 months; HR: 1.417 [95% CI: 1.187, 1.691; p<0.001]).

CONCLUSIONS: ESK-NS patients experienced significantly greater improvements in HRQoL versus QTP‑XR, plus had greater likelihood and speed of meaningful improvement over 32 weeks as measured by the QLDS. These results support the superior short- and long‑term clinical efficacy previously demonstrated for ESK-NS in ESCAPE-TRD.